LncRNA APTR amplification serves as a potential glioma biomarker and promotes glioma progression via miR-6734-5p/ TCF7/LEF1 axis

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2025-02-22 DOI:10.1016/j.ncrna.2025.02.007

Heng Chen , Mengzhen Huang , Jiayi Li , Shanshan Zhang , Cuiyun Sun , Wenjun Luo , Lin Yu

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引用次数: 0

Abstract

Background

Alu-mediated p21 transcriptional regulator (APTR) overexpression is detected in different human cancers; however, few reports have investigated APTR gene amplification conditions. Furthermore, whether APTR amplification is related to glioma malignancy and the underlying mechanism remain unknown.

Methods

APTR amplification and expression levels in 153 glioma samples were analyzed using qPCR. Correlations between APTR and patient prognosis were evaluated using Kaplan-Meier survival and COX regression analyses. Both in vitro and in vivo phenotypic assays were performed to confirm the carcinogenic effects of APTR in glioblastoma (GBM) cells. RNA-sequencing and RNA immunoprecipitation and luciferase reporter assays were performed to confirm APTR as a competing endogenous RNA (ceRNA) and to identify the downstream axis of APTR.

Results

Our results suggest that APTR amplification and overexpression are novel independent diagnostic biomarkers for predicting poor prognosis in patients with gliomas. APTR knockdown significantly repressed the proliferation and invasion of GBM cells, both in vitro and in vivo. APTR was demonstrated to absorb miR-6734-5p and upregulate TCF7 and LEF1 expression. Taken together, these results suggest that APTR promotes the malignant phenotypes of GBM by inducing TCF7 and LEF1 expression.

Conclusion

We identified APTR as a novel prognostic biomarker in patients with gliomas and confirmed that APTR is a ceRNA that promotes glioma progression via the APTR/miR-6734-5p/TCF7/LEF1 axis.

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LncRNA APTR扩增作为潜在的胶质瘤生物标志物，通过miR-6734-5p/ TCF7/LEF1轴促进胶质瘤进展

dalu介导的p21转录调节剂（APTR）过表达在不同的人类癌症中被检测到；然而，很少有研究APTR基因扩增条件的报道。此外，APTR扩增是否与胶质瘤恶性有关及其机制尚不清楚。方法采用qPCR方法对153例胶质瘤标本中saptr的扩增及表达水平进行分析。应用Kaplan-Meier生存期和COX回归分析评估APTR与患者预后的相关性。体外和体内表型分析证实了APTR对胶质母细胞瘤（GBM）细胞的致癌作用。通过RNA测序、RNA免疫沉淀和荧光素酶报告基因测定，证实了APTR是一种竞争性内源性RNA (ceRNA)，并鉴定了APTR的下游轴。结果APTR扩增和过表达是预测胶质瘤患者预后不良的新的独立诊断生物标志物。在体外和体内实验中，APTR敲低均能显著抑制GBM细胞的增殖和侵袭。APTR被证明可以吸收miR-6734-5p并上调TCF7和LEF1的表达。综上所述，这些结果表明APTR通过诱导TCF7和LEF1的表达促进GBM的恶性表型。我们发现APTR是胶质瘤患者的一种新的预后生物标志物，并证实APTR是一种通过APTR/miR-6734-5p/TCF7/LEF1轴促进胶质瘤进展的ceRNA。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.